Liquid chromatography mass spectrometry (“LCMS”) is a powerful analyte detection and measurement technique that has become the preferred method of detecting small molecule, amino acid, protein, peptide, nucleic acid, lipid, and carbohydrate analytes to a high accuracy for diagnostic purposes. However, the instrumentation required for LCMS is technically complex and not well suited to the typical hospital clinical lab or medical lab technician. These clinical labs have not adopted LCMS diagnostics and, instead, generally use alternative diagnostic techniques, including automated immunoassay. Alternatively, the clinical labs may send the samples out to a central reference laboratory for analysis.
Current LCMS methods require careful selection of the appropriate liquid chromatography column and mobile phases for each analyte assay, as well as complex calibration of the mass spectrometer to isolate and identify the analyte of interest. Moreover, in order to analyze a different analyte or different class of analyte on the same instrument, one or more of the column, the mobile phases, the liquid chromatography settings, and/or the mass spectrometer settings must be changed and optimized by the LCMS technologist. Often, individual hardware components, such as the ion source of the mass spectrometer, must be manually re-configured in order to accommodate a different mode of analysis for a particular analyte. Such complicated equipment and sophisticated scientific techniques require very sophisticated LCMS specialist technologists, and heretofore only the large centrally located reference laboratories have been able to use such LCMS equipment for clinical diagnostics.
At each such reference laboratory, because of the time and technical complexity of such equipment adjustments, patient specimens that utilize the same type of assay are generally grouped into large batches and processed serially, in order to avoid the necessity of making manual adjustments that are time consuming and may be prone to produce errors. While this batch mode automation approach may reduce the amount of LCMS technologist intervention, it significantly increases the “time to result” for each specimen. Thus, non-urgent specimens may not be processed for several hours or even days prior to analysis. For time sensitive specimens, for example, for emergency department patients or transplant patients requiring short turnaround time results for immediate treatment decisions, such delays are unacceptable.
Still further, some specimens have a limited shelf-life due to deterioration of one or more analytes or evaporation which distorts the concentration of the analyte. Therefore, there is a set of complex factors that determine how long a specimen of a particular type may be delayed behind other specimens of a higher priority.
For a typical hospital lab, an LCMS system is a very large capital investment. As such, it is often impractical for a hospital lab to purchase multiple systems for different dedicated analyses. Thus, it is impractical for a hospital, even a large one, to use batch mode automation for clinical LCMS application, as it does not have the scale of a central reference laboratory and may be forced to make frequent changes to the LCMS hardware and complex setting, as it switches the testing from one type or class of analytes to another. Faced with the large economic and technical challenges, such clinical labs have been unable to reap the technical benefit of LCMS technologies for routine patient specimens, but have been forced to send patient samples on to the central reference labs.
Therefore, there is a need for sample preparation and sample analysis systems that are more flexible for handling different types of analyte assays. There is also a need for sample preparation and sample analysis systems that are less complex to configure and use for preparing samples and conducting a variety of different analyte assays, without requiring the expertise of LCMS technologists, or the massive scale of a reference laboratory. There is yet also a need for a sample preparation and sample analysis systems that improve the efficiency of the time to result for a variety of different analyte assays.